The lipoxin receptor ALX: potent ligand-specific and stereoselective actions in vivo

Pharmacol Rev. 2006 Sep;58(3):463-87. doi: 10.1124/pr.58.3.4.

Abstract

Lipoxins (LXs) and aspirin-triggered LX (ATL) are trihydroxytetraene-containing eicosanoids generated from arachidonic acid that are distinct in structure, formation, and function from the many other proinflammatory lipid-derived mediators. These endogenous eicosanoids have now emerged as founding members of the first class of lipid/chemical mediators involved in the resolution of the inflammatory response. Lipoxin A(4) (LXA(4)), ATL, and their metabolic stable analogs elicit cellular responses and regulate leukocyte trafficking in vivo by activating the specific receptor, ALX. ALX was the first receptor cloned and identified as a G protein-coupled receptor (GPCR) for lipoxygenase-derived eicosanoids with demonstrated cell type-specific signaling pathways. ALX at the level of DNA has sequence homology to the N-formylpeptide receptor and as an orphan GPCR was initially referred to as the N-formylpeptide receptor-like 1. Although LXA(4) is the endogenous potent ligand for ALX activation, a number of peptides can also activate this receptor to stimulate calcium mobilization and chemotaxis in vitro. In contrast with LXA(4), the counterparts of many of these peptides in vivo remain to be established. The purpose of this review is to highlight the molecular characterization of the ALX receptor and provide an overview of the ALX-LXA(4) axis responsible for anti-inflammatory and proresolving signals in vivo. The information in this review provides further support for the initial nomenclature proposition for this GPCR as ALX.

Publication types

  • Review

MeSH terms

  • Animals
  • Aspirin / pharmacology
  • Cysteine / metabolism
  • Cysteine / physiology
  • Humans
  • Leukotrienes / metabolism
  • Leukotrienes / physiology
  • Ligands
  • Lipids / chemistry
  • Lipoxins / biosynthesis
  • Lipoxins / metabolism
  • Models, Biological
  • Molecular Conformation*
  • Molecular Sequence Data
  • Peptides / chemistry
  • Phylogeny
  • Receptors, Aryl Hydrocarbon / physiology
  • Receptors, Formyl Peptide / metabolism*
  • Receptors, Formyl Peptide / physiology
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Growth Factor / physiology
  • Receptors, Lipoxin / metabolism*
  • Receptors, Lipoxin / physiology
  • Signal Transduction
  • Substrate Specificity

Substances

  • FPR2 protein, human
  • Leukotrienes
  • Ligands
  • Lipids
  • Lipoxins
  • Peptides
  • Receptors, Aryl Hydrocarbon
  • Receptors, Formyl Peptide
  • Receptors, G-Protein-Coupled
  • Receptors, Growth Factor
  • Receptors, Lipoxin
  • cysteinyl-leukotriene
  • lipoxin A4
  • Cysteine
  • Aspirin